6/8/07 DRAFT

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

HUMAN STUDIES REVIEW BOARD (HSRB)

JUNE 27-29, 2007 *

PUBLIC MEETING

Wednesday, June 27, 2007

Environmental Protection Agency 

Conference Center - Lobby Level 

One Potomac Yard (South Bldg.)

2777 S. Crystal Drive

 Arlington, VA 22202 

HSRB WEB SITE   http://www.epa.gov/osa/hsrb/

Docket Telephone: (202) 566 1752

Docket Number: EPA-HQ-ORD-2007-0403

( 8:30 AM	Convene Meeting and Identification of Board Members – Celia
Fisher, Ph.D. (HSRB Chair)

( 8:45 AM	Welcome – George Gray, Ph.D. (EPA Science Advisor) 

( 8:55 AM	Opening Remarks – Debbie Edwards, Ph.D. (Director, Office of
Pesticide Programs, [OPP])

( 9:05 AM	Meeting Administrative Procedures - Paul Lewis, Ph.D.
(Designated Federal Officer [DFO], HSRB, OSA, EPA) 

( 9:10 AM	Meeting Process – Celia Fisher, Ph.D. (HSRB Chair) 

( 9:20 AM	EPA Follow-up on HSRB Recommendations – Mr. William Jordan
(EPA, OPP)   

Review of Draft April 18-20, 2007 HSRB Report

( 9:40 AM	Board Discussion and Decision on Report – Celia Fisher,
Ph.D. (HSRB Chair)

Completed Repellent Efficacy Studies: IR3535 Aerosol (EMD-003.3 and
EMD-004.3)

Carroll-Loye Mosquito Repellent Efficacy Protocol WPC-001

Research Conducted After April 7, 2006: Meaning of “Substantial
Compliance” with 40 CFR Part 26 

	Completed Patch Test Studies

Framework for Developing Best Practices for Subject Recruitment for
Handler Exposure Research

Follow-up on AHETF and AEATF Protocols 

( 11:00 AM	Break

( 11:15 AM	Public Comments 

( 11:30 AM	Summary and Next Steps - Celia Fisher, Ph.D. (HSRB Chair) and
Paul Lewis, Ph.D. (Designated Federal Officer, HSRB, EPA) 

Carroll-Loye Picaridin Mosquito Repellency Protocol LNX-001 

( 11:40 AM	Science and Ethics of Carroll-Loye Protocol –Mr. Kevin
Sweeney (OPP, EPA) and Mr. John Carley (OPP, EPA) 

( 12:20 PM	Lunch  

( 1:30 PM	Public Comments 

( 2:00 PM	Board Discussion 

a. 	If the proposed research described in Protocol LNX-001 from
Carroll-Loye Biological Research is revised as suggested in EPA’s
review, does the research appear likely to generate scientifically
reliable data, useful for assessing the efficacy of the test substances
for repelling mosquitoes? 

b. 	If the proposed research described in Protocol LNX-001 from
Carroll-Loye Biological Research is revised as suggested in EPA’s
review, does the research appear to meet the applicable requirements of
40 CFR part 26, subparts K and L?  

ICR Picaridin Mosquito Repellency Protocol

( 2:45 PM	Science and Ethics of ICR Protocol –Mr. Kevin Sweeney. (OPP,
EPA) and Mr. John Carley (OPP, EPA) 

( 3:45 PM	Public Comments 

( 4:15 PM	Break

( 4:30 PM	Board Discussion   

a. 	If the proposed research described in ICR’s proposed picaridin
protocol is revised as suggested in EPA’s review, does the research
appear likely to generate scientifically reliable data, useful for
assessing the efficacy of the test substances for repelling mosquitoes? 

b. 	If the proposed research described in ICR’s proposed picaridin
protocol is revised as suggested in EPA’s review, does the research
appear to meet the applicable requirements of 40 CFR part 26, subparts K
and L?  

( 5:30 PM	Adjournment  

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

HUMAN STUDIES REVIEW BOARD (HSRB)

JUNE 27-29, 2007 *

PUBLIC MEETING

Thursday, June 28, 2007

Environmental Protection Agency 

Conference Center - Lobby Level 

One Potomac Yard (South Bldg.)

2777 S. Crystal Drive

 Arlington, VA 22202 

( 8:30 AM	Convene Meeting – Celia Fisher, Ph.D. (HSRB Chair)

( 8:40 AM	Follow-up From Previous Day’s Discussion – Mr. William
Jordan (OPP, EPA)  

Acrolein 

( 8:50 AM	Acrolein – Abdallah Khasawinah, Ph.D. (OPP, EPA) and Mr.
John Carley (OPP, EPA) 

( 9:45 AM	Public Comments 

( 10:15 AM	Break

( 10:30 AM	Board Discussion 

a.  	The Agency has concluded that this study contains information
sufficient for assessing human risk resulting from potential acute
inhalation exposure.  Please comment on whether the study is
sufficiently sound, from a scientific perspective, to be used to
estimate a safe level of acute inhalation exposure to acrolein.  

b. Please comment on the following:

(1) Is there clear and convincing evidence that the conduct of the study
was fundamentally unethical?

(2) Is there clear and convincing evidence that the conduct of the study
was significantly deficient relative to the ethical standards prevailing
at the time the research was conducted?

4-Amino Pyridine 

( 11:30 AM	4-Amino Pyridine – Abdallah Khasawinah, Ph.D. (OPP, EPA)
and Mr. John Carley (OPP, EPA) 

( 12:15 PM	Public Comments 

( 12:30 PM	Lunch 

( 1:30 PM	Board Discussion  

a.The Agency’s weight-of-evidence (WOE) document for 4-aminopyridine
describes the study design and results of three clinical trials
(Grijalva et al. 2003, Segal et al. 1999, and Van Diemen et al. 1993). 
The WOE document also discusses the Agency’s conclusion that these
studies provide sufficient information to establish a point of departure
for the assessment of the risk to humans resulting from all potential
durations of exposure to 4-AP.  Please comment on whether the studies
are sufficiently sound, from a scientific perspective, to be used to
derive a point of departure for estimating risk to humans from exposure
to 4-AP.

b.	Please comment on the following:

(1) Is there clear and convincing evidence that the conduct of any of
the clinical studies was fundamentally unethical?

(2) Is there clear and convincing evidence that the conduct of any of
the clinical studies was significantly deficient relative to the ethical
standards prevailing at the time the research was conducted?

( 2:30 PM	Break

AEATF and AHETF Research Programs 

	Introduction

( 2:45 PM	EPA Presentation - William Jordan (EPA, OPP)

	Overview / Risks and Benefits of Handler Research

( 2:50 PM	EPA Presentation –  Mr. John Carley (OPP, EPA)

( 3:30 PM	Public Comments   

( 3:45 PM	Board Discussion  

Risks and Benefits of Handler Research

1). Will the Task Forces’ Governing Documents considered in
conjunction with the additional study- and scenario-specific information
specified above provide an adequate basis for assessing whether the
risks of conducting a particular study are justified by the expected
benefits of the proposed research?  If not, what additional information
should be provided for an IRB, EPA, and the HSRB?

	Addressing Potential Sources of Underestimation Bias/QA and QC Controls


( 5:00 PM	EPA Presentation – Mr. Jeff Dawson (OPP, EPA)  

( 5:30 PM	Public Comments 

( 5:45 PM	Adjournment 

 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

HUMAN STUDIES REVIEW BOARD (HSRB)

JUNE 27-29, 2007 *

PUBLIC MEETING

Friday, June 29, 2007

Environmental Protection Agency 

Conference Center - Lobby Level 

One Potomac Yard (South Bldg.)

2777 S. Crystal Drive

 Arlington, VA 22202 

( 8:30 AM	Convene Meeting – Celia Fisher, Ph.D. (HSRB Chair)

( 8:40 AM	Follow-up From Previous Day’s Discussion – Mr. William
Jordan (OPP, EPA)  

AEATF and AHETF Research Programs: 

	Addressing Potential Sources of Underestimation Bias; QA and QC
Controls (continued)

( 8:50 AM	Board Discussion

Addressing Potential Sources of Underestimation Bias

1) Has EPA appropriately characterized the limitations on the scientific
usefulness of a handler database that does not include data
characterizing the efficiency of residue removal procedures?  If not,
what limitations have been overlooked?

2) Has EPA identified the relevant scientific and practical
considerations affecting the choice to include biomonitoring, and has
EPA appropriately characterized the limitations on the scientific
usefulness of the resulting data if no biomonitoring is conducted?  If
not, what other considerations should bear on a decision to conduct
biomonitoring in addition to WBD?

	QA/QC Controls

1) Do the Task Forces’ Standard Operating Procedures appear adequate
to ensure that the data resulting from the proposed research will be of
high quality?  If not, what other Quality Assurance or Quality Control
procedures need to be addressed?

( 10:00 AM	Break    

	Design of Scenario-Level Sampling; Statistical Justification of Number
of Clusters; and Monitoring Units and Within Worker Variability 

( 10:15 AM	EPA Presentation – Mr. David Miller (OPP, EPA)

( 11:00 AM	Public Comments   

( 11:15 AM	Board Discussion 

Design of Scenario-Level Sampling

With regard to the AHETF and AEATF plans to conduct their proposed
handler research using purposive diversity sampling strategies: 

1) Has EPA identified the relevant scientific and practical
considerations affecting the choice of a strategy for sample selection? 
If not, what other considerations should bear on the choice?

2) Does the HSRB agree with EPA that the Task Forces should provide
scenario-specific information about the availability of data to identify
significant variables (other than AaiH) potentially influencing exposure
and about the feasibility of developing a sampling strategy to address
those variables quantitatively?   If not, what additional information is
needed?

3) Has EPA appropriately characterized the limitations on the scientific
usefulness of the resulting data attributable to the choice of the
sampling strategy?  If not, what has EPA 

overlooked?

Statistical Justification of Number of Clusters

What additional information, if any, would the HSRB need to assess the
adequacy of the justification for the number of clusters and number of
MUs in specific AHETF and AEATF study proposals?

Within-Worker Variability

1. Has EPA appropriately characterized the limitations on the scientific
usefulness of a database that does not include repeated measures?  If
not, what limitations has EPA overlooked?

( 12:15 PM	Lunch  

	Subject Recruitment and Enrollment Issues

( 1:15 PM	EPA Presentation - Mr. John Carley (OPP, EPA)

( 1:45 PM	Public Comments   

( 2:00 PM	Board Discussion 

1. Does the Board agree that the Governing Documents and associated SOPs
of the AHETF and AEATF research programs include comprehensive and
appropriate protections for human subjects of the research?  If not,
what has been overlooked?

2. In singling out the handling of language differences as an area
requiring further refinement, has EPA overlooked other areas in need of
revision?  If so, what?

( 3:00 PM	Adjournment  

Please be advised that agenda times are approximate and subject to
change. For further information, please contact the Designated Federal
Officer for this meeting, Paul Lewis via telephone: (202) 564-8381 or
email:   HYPERLINK "mailto:lewis.paul@epa.gov"  lewis.paul@epa.gov  

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